Colonic NeoplasmsPhase 2ImPACCTNCT02685046
Imatinib as Pre-operative Anti-Colon Cancer Targeted Therapy
A Phase 2 study testing Imatinib in people with Colonic Neoplasms, run by UMC Utrecht at 3 sites in Netherlands.
Trial summary
In this proof-of-concept trial the investigators will study the effects of imatinib treatment on the biology of mesenchymal-type colon cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colonic Neoplasms
- What is being tested?
- Imatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesNetherlands
- Study dates
- Apr 2016to 1 Sep 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged ≥18 years
- Histologically proven adenocarcinoma of the colon;
- Completed cancer staging with CT-abdomen and CT-thorax/X-thorax according to hospital's standard of care;
- Confirmed eligibility for surgery with curative intent as deemed by the hospital's multidisciplinary board (MDB) review;
- An intratumoural gene expression profile of PDGFR-α, PDGFR-β, PDGF-C and KIT, indicative of the mesenchymal phenotype, according to our diagnostic RT-qPCR test (i.e. more than 50% chance of having the mesenchymal phenotype);
- Minimum of four properly stored pre-treatment biopsies for gene expression analysis/ELISA;
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- WHO performance status 0 or 1;
- Adequate haematology status and organ function, defined as:
- Normal creatinine clearance (≥60 ml/min (MRDR))
- ALAT within 2.5x upper limit of normal (ULN)
- PT-INR < 1.5
- Leukocytes > 1,5*10^9/L; Hb > 6.0 mmol/L; platelets > 100*10^9/L
- Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests;
- Written informed consent.
Who cannot join
- The presence of synchronous distant metastases;
- Current hospital standard of care dictates that subject should undergo any neoadjuvant therapy;
- Concurrent participation in another clinical trial using any medicinal product, or participation in such a trial in the period of three months prior to the current trial;
- Women who are pregnant, plan to become pregnant or are lactating during the study or for up to 30 days after the last dose of imatinib;
- Known HIV or Hepatitis B/C infection;
- Known symptomatic congestive heart failure;
- Co-morbidity requiring concomitant treatment with drugs that act as strong inducers of CYP3A4 or with drugs with a narrow therapeutic range influenced by imatinib
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Meander Medical Center
Amersfoort, Utrecht, 3813TZ
Diakonessenhuis
Utrecht, 3582KE
University Medical Center Utrecht
Utrecht, 3584CX
About this study
Official title: Targeted Therapy With Imatinib for Treatment of Poor Prognosis Mesenchymal-type Resectable Colon Cancer: a Proof-of-concept Study in the Preoperative Window Period.
In this proof-of-concept trial the investigators will study the effects of imatinib treatment on the biology of mesenchymal-type colon cancers.
Read the detailed description
Tumor biopsies from patients with newly diagnosed colon cancer will be pre-screened with an RT-qPCR test to identify tumors of the mesenchymal subtype. Patients with mesenchymal-type tumors that meet the in- and exclusion criteria will be treated with imatinib during the "window period" that normally precedes surgery. Immediately following tumor resection, biopsies will be taken from the surgical specimen. Gene and protein expression of the pre- and post-treatments biopsies will be compared to assess the effects of imatinib therapy on PDGFR- and cKIT-signalling and on the mesenchymal gene expression profile.
- Conditions
- Colonic Neoplasms
- Being tested
- Imatinib
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Also called Gleevec, STI571
Subjects will be treated with the medicinal product imatinib, which will be administered orally in tablets of 400mg, once per day, during two weeks prior to tumor resection.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Subjects will be treated with the medicinal product imatinib, which will be administered orally in tablets of 400mg, once per day, during two weeks prior to tumor resection. Receives: Drug: Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of treatment on the mesenchymal gene expression profile
To assess the extent of change in the mesenchymal phenotype, gene expression arrays will be generated from pre- and post-treatment tissue samples and the expression of genes associated with the poor-prognosis mesenchymal subtype will be compared.
Measured: period from diagnostic colonoscopy until surgical resection (~5 weeks)
Secondary outcomes (7)
Extent of targeted inhibition of PDGFR and KIT phosphorylation in cancer cells
- Measurement of PDGFR and cKIT inhibition by comparison of the fraction of autophosphorylated PDGFR and cKIT pre-treatment versus post-treatment, measured with ELISA on tissue samples derived from diagnostic biopsies and surgery.
Measured: period from diagnostic colonoscopy until surgical resection (~5 weeks)
Correlation between plasma imatinib trough levels on day 14 and intratumoural concentration of imatinib in the resection specimen
Measured: at time of surgery
Correlation between the extent of PDGFR and cKIT inhibition and systemic and intratumoural imatinib and CGP74588 concentration
Measured: at time of surgery
Change in plasma CEA-concentrations
Measured: period between diagnostic colonoscopy until surgical resection (~5 weeks)
Change in plasma levels of circulating tumor DNA
Measured: period between diagnostic colonoscopy until surgical resection (~5 weeks)
Effects of imatinib on the ability of cancer cells to form in vitro 3D cell cultures (organoids)
- The ability to establish organoids from imatinib-treated tumours will be compared with the general success rate of organoid formation from colon tumours at the Hubrecht Institute.
Measured: at time of surgery
Number of participants with treatment-related adverse events as assessed by CTCAEv4.02
The occurrence, frequency and severity of adverse events during preoperative treatment with imatinib, peroperatively or in the postoperative period (up to 14 days after tumour resection).
Measured: from start of treatment until 2 weeks after last dose imatinib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2016 (estimated)
- Study startApr 2016
- Primary completion1 Sep 2019
- Study completion1 Sep 2019
Why it stopped: Low accrual rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colonic NeoplasmsStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Meander Medical Center, Erasmus Medical Center, Hubrecht Institute
- Responsible party
- Principal investigator, Prof dr I.H.M. Borel Rinkes, UMC Utrecht
- Investigators
- I HM Borel Rinkes, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685046
- Sponsor's protocol ID
- CC-TT-IMA-14
- Other IDs
- NL50620.041.15, 2014-003965-11, 2014
- Acronym
- ImPACCT
- Status last verified
- Oct 2019
- First submitted
- 9 Feb 2016
- Last updated
- 14 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Ubink I, Bloemendal HJ, Elias SG, Brink MA, Schwartz MP, Holierhoek YCW, Verheijen PM, Boerman AW, Mathijssen RHJ, de Leng WWJ, de Weger RA, van Grevenstein WMU, Koopman M, Lolkema MP, Kranenburg O, Borel Rinkes IHM. Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a proof-of-concept study in the preoperative window period (ImPACCT). BMC Cancer. 2017 Apr 19;17(1):282. doi: 10.1186/s12885-017-3264-y.
PubMed 28424071
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Therapy With Imatinib for Treatment of Poor Prognosis Mesenchymal-type Resectable Colon Cancer: a Proof-of-concept Study in the Preoperative Window Period.
- ClinicalTrials.gov ID
- NCT02685046
- Acronym / sponsor ID
- ImPACCT / CC-TT-IMA-14
- Conditions
- Colonic Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual rate
- Enrolment
- 5 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Meander Medical Center, Erasmus Medical Center, Hubrecht Institute
- Study start
- Apr 2016
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 1 Sep 2019 (actual)
- First posted
- 18 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this proof-of-concept trial the investigators will study the effects of imatinib treatment on the biology of mesenchymal-type colon cancers.
Detailed description
Tumor biopsies from patients with newly diagnosed colon cancer will be pre-screened with an RT-qPCR test to identify tumors of the mesenchymal subtype. Patients with mesenchymal-type tumors that meet the in- and exclusion criteria will be treated with imatinib during the "window period" that normally precedes surgery. Immediately following tumor resection, biopsies will be taken from the surgical specimen. Gene and protein expression of the pre- and post-treatments biopsies will be compared to assess the effects of imatinib therapy on PDGFR- and cKIT-signalling and on the mesenchymal gene expression profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: ImatinibSubjects will be treated with the medicinal product imatinib, which will be administered orally in tablets of 400mg, once per day, during two weeks prior to tumor resection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female aged ≥18 years
- Histologically proven adenocarcinoma of the colon;
- Completed cancer staging with CT-abdomen and CT-thorax/X-thorax according to hospital's standard of care;
- Confirmed eligibility for surgery with curative intent as deemed by the hospital's multidisciplinary board (MDB) review;
- An intratumoural gene expression profile of PDGFR-α, PDGFR-β, PDGF-C and KIT, indicative of the mesenchymal phenotype, according to our diagnostic RT-qPCR test (i.e. more than 50% chance of having the mesenchymal phenotype);
Key exclusion criteria (7 listed)
- The presence of synchronous distant metastases;
- Current hospital standard of care dictates that subject should undergo any neoadjuvant therapy;
- Concurrent participation in another clinical trial using any medicinal product, or participation in such a trial in the period of three months prior to the current trial;
- Women who are pregnant, plan to become pregnant or are lactating during the study or for up to 30 days after the last dose of imatinib;
- Known HIV or Hepatitis B/C infection;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImatinibAlso: Gleevec, STI571Subjects will be treated with the medicinal product imatinib, which will be administered orally in tablets of 400mg, once per day, during two weeks prior to tumor resection. | Drug | Intervention |
Primary outcome
Effects of treatment on the mesenchymal gene expression profile
Time frame: period from diagnostic colonoscopy until surgical resection (~5 weeks)
To assess the extent of change in the mesenchymal phenotype, gene expression arrays will be generated from pre- and post-treatment tissue samples and the expression of genes associated with the poor-prognosis mesenchymal subtype will be compared.
7 secondary outcomes
Extent of targeted inhibition of PDGFR and KIT phosphorylation in cancer cells
Time frame: period from diagnostic colonoscopy until surgical resection (~5 weeks)
Correlation between plasma imatinib trough levels on day 14 and intratumoural concentration of imatinib in the resection specimen
Time frame: at time of surgery
Correlation between the extent of PDGFR and cKIT inhibition and systemic and intratumoural imatinib and CGP74588 concentration
Time frame: at time of surgery
Change in plasma CEA-concentrations
Time frame: period between diagnostic colonoscopy until surgical resection (~5 weeks)
Change in plasma levels of circulating tumor DNA
Time frame: period between diagnostic colonoscopy until surgical resection (~5 weeks)
Effects of imatinib on the ability of cancer cells to form in vitro 3D cell cultures (organoids)
Time frame: at time of surgery
Number of participants with treatment-related adverse events as assessed by CTCAEv4.02
Time frame: from start of treatment until 2 weeks after last dose imatinib
Results and safety
The study was stopped early (reason given: Low accrual rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2019.
- Derived from this study: PubMed 28424071Ubink I, Bloemendal HJ, Elias SG, Brink MA, Schwartz MP, Holierhoek YCW, Verheijen PM, Boerman AW, Mathijssen RHJ, de Leng WWJ, de Weger RA, van Grevenstein WMU, Koopman M, Lolkema MP, Kranenburg O, Borel Rinkes IHM. Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a proof-of-concept study in the preoperative window period (ImPACCT). BMC Cancer. 2017 Apr 19;17(1):282. doi: 10.1186/s12885-017-3264-y.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
I HM Borel Rinkes, MD, PhD principal investigator
UMC Utrecht
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib in people with Colonic Neoplasms, run by UMC Utrecht at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual rate). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of treatment on the mesenchymal gene expression profile (time frame: period from diagnostic colonoscopy until surgical resection (~5 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02685046, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2019.